Thermodynamic descriptors derived from density functional theory calculations in prediction of aquatic toxicity

Ab initio Density Functional Theory methods at the B3LYP/6-311+G(2d,p)//HF/3-21G(d) level in the gas and solvent phases (Conductor-like Polarizable Continuum Model) were used to calculate the thermodynamic and charge related descriptors including the first-order dissociation constant for a set of 53 substituted phenols. The absolute values of the pKa DFT descriptor showed significant deviations from the experimental values of dissociation constants, but the relative trends were well-described (R2=0.929, n=40). The descriptors were used for the design of predictive models for two aquatic species Pimephales promelas and Tetrahymena pyriformis. In both cases the best performing 2-descriptor models were based on the descriptors DeltaH298gas) and ClogP and showed good predictivity with R2=0.853, R2CV=0.834 for Pimephales and R2=0.864, R2CV=0.833 for Tetrahymena. The descriptors, models and the mode of action of the compounds are discussed.